Vanek was a member of the Austrian national team in the 2004 IIHF World Championships, where he collected seven points in six games (two goals and five assists). Vanek led the Golden Gophers in goals (26) and points (51) for the second-straight season and finished fifth in points among Division I leaders with 51. Vanek was the Twin Cities Best College Athlete for 2004.[citation needed]

Vanek spent 2004–05 with the Sabres' American Hockey League (AHL) affiliate, the Rochester Americans, recording 68 points in 74 games and helped Rochester to the best record in the AHL. Vanek finished second on the team in points, 11 points behind Chris Taylor, but led the team in goals with 42 and in power play goals with 25. He finished second among rookies in points and led all rookies in goals scored, the latter of which was second in the league among all players.

Vanek signed a three-year deal with Buffalo on 3 September 2004,[5] and began playing for the Sabres in 2005–06 after a season with their AHL affiliate. He had a promising rookie season with 25 goals and 48 points in 81 games for the Sabres. His performance tailed off in the playoffs, managing two goals in ten games.

Vanek recorded his best statistical season, the following year in 2006–07. He played in all 82 regular season games for the Sabres, scoring 43 goals, tied for fifth in the league, and 41 assists. He also finished an NHL best +47, earning the NHL Plus-Minus Award. Upon the expiration of his entry-level contract during the 2007 off-season, Vanek signed a seven-year, $50 million offer sheet from the Edmonton Oilers.[6] The Sabres, having lost Chris Drury and Daniel Brière as free agents that off-season, immediately matched the offer sheet, thus keeping Vanek under contract until at least the end of the 2013–14 season.[7] Despite his lucrative new contract, Vanek's production dipped to 64 points in 2007–08.

Vanek in October 2006 playing for the Buffalo Sabres

In the midst of a more productive year, however, Vanek was named to his first NHL All-Star Game in 2009 in Montreal.[8] He helped the East to a 12–11 shootout victory over the West. Earlier in the season, on 13 December 2008, Vanek helped the Sabres reach a milestone by scoring the 10,000th goal in franchise history. Following the All-Star Game, on 4 February 2009, Vanek made NHL history by becoming only the second player to score four consecutive natural hat-trick.[9] He recorded his fourth natural hat trick, and fifth overall, in a 5–0 win over the Toronto Maple Leafs in HSBC Arena.[9] It was also Vanek's fourth consecutive natural hat-trick, matching an NHL record set by Cy Denneny between 1923 and 1924 with the old Ottawa Senators. Later that week, on 7 February, Vanek took a slapshot from Anton Volchenkov of the Ottawa Senators, fracturing his jaw. He underwent surgery the next day and was announced to be out of the lineup for three-to-four weeks.[9] At the time of the injury, Vanek was third in the league goal-scoring. At the end of the 2008–09 season, Vanek would score a total of 40 goals with 24 assists, totaling 64 points. He led the NHL in powerplay goals with 20.[10]

The 2009–10 season also started on a sour note, as Vanek sustained an upper body injury after scoring two goals in a 6–2 win against the Detroit Red Wings on 13 October.[11] Vanek had scored three goals in four games up to that point. On 10 April 2010, he scored four goals against Ottawa (one on a penalty shot) in the first two periods.[12]

On 27 October 2013, Vanek was traded to the New York Islanders for Matt Moulson, a conditional 2014 first-round draft pick and a 2015 second-round draft pick.[16] He immediately joined the team's top line alongside John Tavares and Kyle Okposo, which Vanek said later was the best line he ever played on.[17][18] On 4 February 2014, Vanek confirmed that he had turned down a contract extension offer from the Islanders. The contract was reportedly for seven years and $50 million, with Vanek stating that the Islanders move to Barclays Center was one of his primary reasons for leaving the team.[17][19]

On 5 March 2014, Vanek was dealt to the Montreal Canadiens in exchange for Sebastian Collberg and a second-round draft pick.[20] On 19 March 2014, he scored his first three goals for the team – a hat trick in a game against the Colorado Avalanche that they went on to win 6–3.[21] However, Vanek was noted for his lackluster performance during the 2014 Stanley Cup playoffs, including scoring just five even-strength points over 17 games.[22] In late June, Canadiens General Manager Marc Bergevin announced that the team would not be re-signing Vanek, allowing him to become an unrestricted free agent.[22]

On 1 July 2014, Vanek signed a three-year, $19.5 million contract with the Minnesota Wild with a no-trade clause, turning down a three-year, $21 million offer to return to the Islanders.[23][24] The signing reunited Vanek with former Sabres teammate Jason Pominville.

With the Wild up against the salary cap and Vanek having endured an unsuccessful stint with the Wild, Vanek's last year of his contract was bought-out by Minnesota on 24 June 2016.[25]

With the Panthers looking to make a playoff push, on 1 March 2017, Vanek was traded to the Florida Panthers in exchange for Dylan McIlrath and a conditional third-round pick in the 2017 NHL Entry Draft.[26][27] Vanek recorded 10 points in 20 games with Florida, but ultimately the Panthers did not qualify for the post-season.

On 21 July 2014, Vanek's name was listed in records seized from The Marina Restaurant & Bar, a Rochester, New York, facility suspected of running an illegal gambling ring. For his part, Vanek denies all wrongdoing, is cooperating with authorities and does not expect to be charged with any crime.[34]